Stereoselective TiCl4-mediated aldol reactions starting from acylsilanes

Article abstract of DOI:10.1002/ejoc.201403263

A simple and efficient method for the preparation of β-hydroxyacylsilanes has been developed through a TiCl₄-mediated aldol reaction. A selection of Lewis acids has been assessed, and other parameters such as solvent and temperature have been optimized. These aldol reactions occur under mild conditions and furnish a selection of β-hydroxy acylsilanes in fair-to-good yields with high syn selectivities (up to 99%).

Full text of DOI:10.1002/ejoc.201403263

Job/Unit: O43263
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Date: 15-12-14 13:03:59
Pages: 8
FULL PAPER
DOI: 10.1002/ejoc.201403263
Stereoselective TiCl4-Mediated Aldol Reactions Starting from Acylsilanes
Gangababu Marri,[a] J. Satyanarayana Reddy,[a] Johal Ruiz,[b] Saibal Das,*[a] and
René Grée*[b]
Keywords: Silanes / Aldol reactions / Silicon / Lewis acids
A simple and efficient method for the preparation of β-
hydroxyacylsilanes has been developed through a TiCl4-me-
diated aldol reaction. A selection of Lewis acids has been
assessed, and other parameters such as solvent and tempera-
ture have been optimized. These aldol reactions occur under
mild conditions and furnish a selection of β-hydroxy acylsil-
anes in fair-to-good yields with high syn selectivities (up to
99%).
in the presence of 1 equiv. of Et3N.[12] On the other hand,
some direct aldol reactions were carried out with TiCl4
alone in the absence of a base.[13] Further, for unsymmetri-
cal ketones, reactions with substoichiometric amounts of
TiCl4 at room temperature gave aldol products at the most-
hindered side of the starting ketone in good yields and with
excellent syn selectivity.[13b] Then, an efficient method was
developed with a combination of TiCl4, Bu3N and a cata-
lytic amount of trimethylsilyl chloride (TMSCl).[14]
To the best of our knowledge, similar direct acid-medi-
ated aldol-type reactions starting from acylsilanes have
never been described. The goal of this publication is to
demonstrate that efficient direct aldol reactions can be
achieved in good diastereoselectivities with acylsilane start-
ing materials and TiCl4 as the most-efficient Lewis acid.
Introduction
Acylsilanes are highly versatile intermediates in organic
synthesis.[1] In particular, β-hydroxy- and β-alkoxyacylsil-
anes are very attractive building blocks with high synthetic
potential. However, only a limited number of protocols
have been reported to date for the synthesis of such inter-
mediates. Starting from acylsilanes, aldolization reactions
mediated by lithium diisopropylamide (LDA) gave the de-
sired products in moderate yields and selectivity.[2] Mukai-
yama aldol reactions,[3] tandem aldol-Tischenko reac-
tions,[4] and boron enolate mediated reactions[5] have been
also reported. Our groups have recently described a new
approach from α-hydroxyallylsilanes that employs a tandem
isomerization–aldolization sequence.[6]
We envisaged a complementary process to prepare these
key intermediates through direct acid-mediated reactions.
TiCl4 has often been used as a Lewis acid catalyst in aldol
reactions, especially with esters[7] or amide derivatives,[8] as
well as in Mukaiyama aldol reactions.[9] It is also very use-
ful in cross aldol reactions starting from aldehydes.[10] For
ketones, several reports have indicated that the results are
strongly dependent upon the structure of the ketone and
the reaction conditions. With preformed titanium enolates,
the aldolization reactions were achieved smoothly at low
temperature at the less-hindered part of the starting ketone
to afford the desired aldols in good yields with excellent
syn selectivity.[11] For acetophenone derivatives, the reaction
could be successfully performed with TiCl4 at 0 °C but only
Results and Discussion
As a model compound, we selected acylsilane 1, which is
readily prepared by a procedure reported by Scheidt.[15] On
the basis of the data mentioned above, we first screened the
conditions for the reaction of this derivative and benzalde-
hyde (2a) with TiCl4 and several other Lewis acids, and the
results are given in Scheme 1 and Table 1.
We initially observed that TiCl4 alone in toluene was able
to promote the aldol reaction to afford the desired products
3a (syn) and 3a (anti) in 85% yield after 1 h at 0 °C, albeit
as a 1:1 mixture (Table 1, Entry 1). Acetonitrile could also
be used as the solvent (Table 1, Entry 2), and methanol gave
a slower reaction and a lower yield (Table 1, Entry 3). On
the other hand, neither CH2Cl2 (Table 1, Entry 4) nor N,N-
dimethylformamide (DMF; Table 1, Entry 5) could be em-
ployed as the solvent for this reaction. Finally, the crucial
role of the titanium reagent was confirmed through the use
of other Lewis acids: no reactions were observed with
BF3·OEt2, ZnCl2 or SnCl4, whereas only traces of aldol
products were found with AlCl3 (Table 1, Entries 6–10).
[a] Natural Product Chemistry Division, CSIR – Indian Institute
of Chemical Technology,
Uppal Road, Tarnaka, Hyderabad 500007, India
E-mail: saibal@iict.res.in
www.iictindia.org
[b] Université de Rennes 1, Institut des Sciences Chimiques de
Rennes, CNRS UMR 6226,
Avenue du Général Leclerc, 35042 Rennes Cedex, France
E-mail: rene.gree@univ-rennes1.fr
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201403263.
Eur. J. Org. Chem. 0000, 0–0
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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G. Marri, J. S. Reddy, J. Ruiz, S. Das, R. Grée
FULL PAPER
Scheme 1. Screening of Lewis acid mediated aldol reaction starting from acylsilane 1.
Table 1. Screening of Lewis acids and solvents.
action was observed with Et3N or diisopropylethylamine
(DIPA) alone (Table 3, Entries 2 and 3). Further, by per-
forming the reaction by the preformed enolate method,[10]
aldols 3a (syn) and 3a (anti) were obtained in moderate
yield in an 80:20 ratio (Table 3, Entry 4). The NMR spec-
troscopic data of these derivatives match perfectly with the
literature values.[2]
Entry Solvent
Lewis acid Temp.
Time [h]
Yield [%]
1
2
3
4
5
6
7
8
9
10
toluene
CH3CN
MeOH
CH2Cl2
DMF
toluene
toluene
CH2Cl2
toluene
toluene
TiCl4
TiCl4
TiCl4
TiCl4
TiCl4
0 °C
0 °C
0 °C
0 °C, r.t.
0 °C, r.t.
1
1.5
24
12
85
75
50
10
–
48
BF3·Et2O 0 °C, r.t.
Ͼ48
Ͼ48
Ͼ48
Ͼ48
Ͼ48
–
Table 3. Different bases tested.[a]
AlCl3
TiCl4
ZnCl2
SnCl4
0 °C, r.t.
r.t.
0 °C, r.t.
0 °C, r.t.
trace
–
–
Entry Base Lewis acid Temp.
Time syn/anti Yield [%]
–
1
2
3
4
Et3N
Et3N
DIPA
LDA
TiCl4
–23 °C
40 min 85:15
85
0
0
–
–
–
–23 °C, 0 °C, r.t.
–23 °C, 0 °C, r.t.
–73 to 0 °C
2 d
2 d
4 h
–
–
80:20
40
As the stereoselectivity was not satisfactory, the reaction
conditions were optimized next for 1 and 2a. At –23 °C, the
reaction was complete after 3.5 h and still afforded a good
yield of 3a but with excellent 95:5 syn selectivity (Table 2,
Entry 1). The reaction could also be performed with sub-
stoichiometric quantities of TiCl4 (Table 2, Entries 2–4;
0.75, 0.50 and 0.25 equiv.), but the time required to com-
plete the reaction increased to 16.5 h, and the yields
dropped to 45%, together with a slight decrease in selectiv-
ity.
[a] Reactions performed with 1 and 2a; toluene was used as the
solvent for each reaction.
Thus, it can be noticed that the aldol reaction does not
require any additional base when these acylsilanes are used
as the nucleophilic component. A similar result has been
reported for some TiCl4-mediated aldolization reactions of
ketones,[13a] whereas the addition of a base was required for
cross aldol reactions with enolizable aldehydes.[10] On the
basis of the similarity of the reaction conditions and dia-
stereoselectivities, it can be anticipated that the mechanism
of the reactions with these acylsilanes should be close to
those proposed for the corresponding ketones.[13]
As the use of 1 equiv. of TiCl4 in toluene at –23 °C ap-
peared to be the best compromise in terms of reactivity and
selectivity, these conditions were employed to study the
scope of the reaction. The results are indicated in Scheme 2
and Table 4.
Table 2. Optimization of reaction conditions.[a]
Entry Equiv. of TiCl4
Time [h]
Yield [%]
syn/anti
1
2
3
4
1.00
0.75
0.50
0.25
3.5
7
9
73
63
60
45
95:5
91:9
90:10
80:20
16.5
[a] Reactions performed with 1 and 2a at –23 °C.
The possible use of various amines in combination with
With aromatic aldehydes, the reaction was compatible
TiCl4 was also examined. Under the same conditions, the with nitro groups at the para (Table 4, Entry 2) and meta
addition of 1 equiv. of Et3N increased the reaction rate, but positions (Table 4, Entry 3) to afford aldols in fair yields
the selectivity decreased to 85:15 (Table 3, Entry 1). No re- with excellent syn selectivities. Similar results were obtained
Scheme 2. TiCl4-mediated aldolizations starting from acylsilane 1.
2
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Stereoselective TiCl4-Mediated Aldol Reactions
Table 4. Various substrates in TiCl4-mediated aldol reactions.[a]
Table 5. TiCl4-mediated aldol reactions with various acylsilanes.
Entry
R
Product Time [h] Yield [%] syn/anti
Entry
Substrate
Yield [%]
Product
syn/anti
1
2
3
4
5
6
7
8
9
Ph
3a
3b
3c
3d
3e
3f
3.5
5
5
5
4.5
4
3
9
14
2
73
60
65
60
55
65
75
30
traces
35
95:5
97:3
95:5
95:5
96:4
89:11
94:6
81:19
83:17
98:2
1
2
3
4
4
5
6
7
70
60
8
9
10
11
83:17
84:16
77:23
99:01
p-O2NC6H4
m-O2NC6H4
p-CNC6H4
p-FC6H4
p-ClC6H4
m-MeOC6H4
p-MeC6H4
p-MeOC6H4
(CH3)2CH
58
45[a]
[a] The addition of Et3N was required. Less than 30% yield without
Et3N.
3g
3h
3i
Conclusions
10
3j
We have developed a new, simple and efficient TiCl4-
mediated aldol reaction starting from easily accessible acyl-
silanes. This protocol opens up new prospects for the use
of acylsilanes in organic chemistry. The extension of this
reaction to asymmetric catalysis and the synthetic applica-
tions of such β-hydroxyacylsilanes are under active study in
our groups.
[a] Acylsilane and RCHO shown in Scheme 2.
with p-cyanobenzaldehyde, p-fluorobenzaldehyde and p-
chlorobenzaldehyde (Table 4, Entries 4–6, respectively), al-
though the selectivity was slightly lower in the later case.
The reaction worked well with m-methoxybenzaldehyde
(Table 4, Entry 7), but low yields were obtained with p-tol-
ylaldehyde (Table 4, Entry 8) and p-methoxybenzaldehyde
(Table 4, Entry 9). Finally, the reaction was compatible with Experimental Section
alkyl-substituted aldehydes, but isobutyraldehyde gave the
General Information: All anhydrous reactions were performed in
aldol products in 35% yield only, albeit with an excellent
98:2 selectivity. All of these derivatives have physical and
analytical data in agreement with their structures. In par-
ticular, the syn isomers have 3JH,H values of ca. 3 Hz, where
oven-dried round-bottomed flasks under a dry argon atmosphere.
Air- and moisture-sensitive compounds were introduced with syrin-
ges or cannulae by using standard inert-atmosphere techniques.
The reactions were monitored by thin layer chromatography (TLC)
with silica gel plates (Merck), and the components were visualized
by illumination with short-wavelength UV light or staining (p-anis-
aldehyde or basic KMnO4). All reagents were used as received from
commercial suppliers, unless otherwise noted. Tetrahydrofuran
(THF) and Et2O were dried in the presence of sodium metal with
benzophenone as an indicator and distilled before use. Anhydrous
CH2Cl2 was prepared under reflux in the presence of CaH2 and
distilled immediately before use. 1H NMR spectra were recorded at
300, 400 and 500 MHz, and 13C NMR spectra were recorded at 75
and 100 MHz with samples in CDCl3. The residual peak of CHCl3
was set at δ = 7.26 ppm for 1H NMR spectroscopy, and the central
3
the anti isomers have JH,H values of ca.7 Hz.
Next, we evaluated the extension of this reaction to other
acylsilanes.[16] This has been achieved with a few, selected
examples as indicated in Scheme 3 and Table 5. For the re-
actions of benzaldehyde with acylsilanes 4–7, the aldol
products 8a–11a were obtained in fair-to-good yields with
good-to-excellent syn/anti selectivities (Table 5). Notably,
the selectivity for the formation of 11a (syn/anti) was 99:01,
but the yield was less than 30%. The yield was improved to
45% by the addition of Et3N (1 equiv.) to the reaction mix-
1
ture. The selectivity ratios were clearly observed in the H peak of CDCl3 was set at δ = 77.0 ppm for 13C NMR spectroscopy.
All products were purified by silica gel flash column chromatog-
raphy (100–200 mesh).
NMR spectra as signals for the major and minor isomers
for all entries.[17]
General Experimental Procedure for the Synthesis of Acylsilanes
from Morpholine Amides: The morpholine amide (2 mmol) was
added to a flame-dried 50 mL round-bottomed flask under dry
nitrogen. To this amide, THF (3 mL) was added, and the solution
was then cooled to –78 °C. Dimethylphenylsilyllithium (1.0 m solu-
tion in THF, 3 mL) was added dropwise with a syringe, and the
reaction mixture stirred for 1.5 h, after which it was quenched at
–78 °C (this is very important to prevent decomposition) by the
addition of saturated aqueous ammonium chloride (4 mL). The re-
sulting heterogeneous mixture was warmed to room temperature
and then stirred for an additional 30 min. The reaction was then
partitioned between water (5 mL) and diethyl ether (5 mL), the
phases were separated, and the aqueous phase was extracted with
diethyl ether (2ϫ5 mL). The combined organic layers were washed
with water (2ϫ20 mL) and brine (20 mL), dried with anhydrous
MgSO4, filtered and concentrated in vacuo. The residue was puri-
fied by silica gel flash column chromatography with the indicated
solvent system to yield pure acylsilane.
1-[Dimethyl(phenyl)silyl]propan-1-one (1): Purified with 4% EtOAc/
Scheme 3. TiCl4-mediated aldol reactions of acylsilanes 4–7.
hexane to afford 1 in 60% yield as a colourless oil. IR: ν = 2969,
˜
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G. Marri, J. S. Reddy, J. Ruiz, S. Das, R. Grée
FULL PAPER
1643, 1428, 1250, 1110, 815, 734, 699 cm–1. 1H NMR (300 MHz, J = 3.2, 7.2 Hz, 1 H), 0.81 (d, J = 7.17 Hz, 3 H), 0.53 (s, 3 H), 0.49
CDCl3): δ = 7.58–7.53 (m, 2 H), 7.42–7.34 (m, 4 H), 2.6 (q, J =
(s, 3 H), 0.42 (s, minor) ppm. 13C NMR (75 MHz, CDCl3): δ =
7.1 Hz, 2 H), 0.89 (t, J = 7.1 Hz, 3 H), 0.49 (s, 6 H) ppm. 13C 250.3 (major), 148.3 (major), 144.3 (major), 133.9 (major), 133.5
NMR (125 MHz, CDCl3): δ = 244.4, 134.4, 133.7, 129.6, 127.9,
41.6, 6.0, –4.8 ppm. HRMS (ESI+): calcd. for C11H20ONSi [M +
NH4]+ 210.1305; found 210.1304.
(major), 131.9 (major), 130.3 (major), 128.8 (major), 128.4 (major),
128.2 (minor), 121.9 (major), 120.8 (major), 70.9 (major), 55.5
(major), 55.4 (minor), 8.0 (major), –4.5 (major), –4.6 (minor), –4.8
(major) ppm. HRMS (ESI+): calcd. for C19H21O4NNaSi [M + Na]+
366.1132; found 366.1141.
1-[Dimethyl(phenyl)silyl]-3-hydroxy-2-methyl-3-phenylpropan-1-one
(3a): By the general experimental procedure for the preparation of
β-hydroxyacylsilanes, the reaction was performed with 1 (100 mg,
4-{3-[Dimethyl(phenyl)silyl]-1-hydroxy-2-methyl-3-oxoprop-
0.52 mmol), benzaldehyde (0.052 mL, 0.52 mmol) and TiCl4 yl}benzonitrile (3d): By the general experimental procedure for the
(0.52 mL, 0.52 mmol) in toluene (5 mL). The conversion of the
acylsilane to the corresponding β-hydroxyacylsilane required 3.5 h
at –30 °C. The crude product was purified by silica gel column
chromatography with 8% ethyl acetate in hexane to afford pure
preparation of β-hydroxyacylsilanes, the reaction was performed
with 1 (100 mg, 0.52 mmol), 4-cyanobenzaldehyde (75 mg,
0.52 mmol) and TiCl4 (0.52 mL, 0.52 mmol) in toluene (5 mL). The
conversion of the acylsilane to the corresponding β-hydroxyacylsil-
ane required 5 h at –30 °C. The crude product was purified by silica
liquid 3a (112 mg, 73% yield) as an inseparable mixture with 95:5
1
(syn/anti) diastereoselectivity. H NMR (300 MHz, CDCl3): δ = gel column chromatography with 10% ethyl acetate in hexane to
7.53 (dd, J = 1.5, 6 Hz, 2 H), 7.46–7.2 (m, 8 H), 7.15 (d, J = 6.7 Hz, afford pure liquid 3d (98 mg, 60% yield) as an inseparable mixture
2 H), 4.99 (d, J = 3.7 Hz, 1 H, major), 4.71 (d, J = 8.3 Hz, minor),
3.3 (pent, J = 7.5 Hz, minor), 3.17 (qd, J = 3.77, 7.5 Hz, 1 H), 2.90
(br, 1 H), 2.6–2.54 (m, minor), 1.26 (s, minor), 084 (d, J = 7.5 Hz,
3 H, major), 0.49 (s, 3 H, major), 0.46 (s, minor), 0.45 (s, major),
0.41 (s, minor) ppm. 13C NMR (75 MHz, CDCl3): δ = 252.5
with 95:5 (syn/anti) diastereoselectivity. 1H NMR (500 MHz,
CDCl3): δ = 7.53 (m, 4 H), 7.48–7.38 (m, 3 H), 7.25 (d, J = 7.9 Hz,
2 H), 5.02 (d, J = 2.8 Hz, 1 H), 4.75 (br, minor), 4.5 (d, J = 5.5 Hz,
minor), 3.32–3.24 (m, minor) 3.19 (br, 1 H), 3.11 (qd, J = 3.0,
7.3 Hz, 1 H), 0.94 (d, J = 6.8 Hz, minor), 0.80 (d, J = 7.3 Hz, 3
(minor), 251.5 (major), 142.4 (minor), 141.9 (major), 133.9 (major), H), 0.57 (s, minor), 0.53 (s, 3 H), 0.49 (s, 3 H), 0.47 (s, minor), 0.41
132.9 (minor), 130.0 (major), 129.8 (minor), 128.2 (major), 128.0
(s, minor) ppm. 13C NMR (75 MHz, CDCl3): δ = 250.8 (major),
(major), 127.7 (minor), 127.6 (minor), 127.0 (major), 126.4 (major), 147.3 (major), 133.8 (major), 133.5 (minor), 131.9 (minor), 131.8
125.8 (major), 71.8 (major), 70.2 (minor), 56.1 (major), 12.8 (major), 130.2 (major), 130.0 (minor), 128.3 (major), 128.1 (minor),
(minor), 8.2 (major), 0.064 (minor), 4.65 (major), 4.878 (major)
126.9 (minor), 126.5 (major), 118.7 (major), 110.7 (major), 71.2
ppm. HRMS (ESI+): calcd. for C18H26O2NSi [M + NH4]+ (major), 60.3 (minor), 55.4 (major), 7.9 (major), –4.7 (major), –4.9
316.1727; found 316.1702.
(major) ppm. HRMS (ESI+): calcd. for C19H21O2NNaSi [M + Na]+
346.1229; found 346.1231.
1-[Dimethyl(phenyl)silyl]-3-hydroxy-2-methyl-3-(4-nitrophenyl)prop-
an-1-one (3b): By the general experimental procedure for the prepa-
ration of β-hydroxyacylsilanes, the reaction was performed with 1
(100 mg, 0.52 mmol), 4-nitrobenzaldehyde (78 mg, 0.52 mmol) and
1-[Dimethyl(phenyl)silyl]-3-(4-fluorophenyl)-3-hydroxy-2-methyl-
propan-1-one (3e): By the general experimental procedure for the
preparation of β-hydroxyacylsilanes, the reaction was performed
TiCl4 (0.52 mL, 0.52 mmol) in toluene (5 mL). The conversion of with 1 (100 mg, 0.52 mmol), 4-fluorobenzaldehyde (0.06 mL,
the acylsilane to the corresponding β-hydroxyacylsilane required
5 h at –30 °C. The crude product was purified by silica gel column
chromatography with 10% ethyl acetate in hexane to afford pure
liquid 3b (100 mg, 60% yield) as an inseparable mixture with 97:3
0.52 mmol) and TiCl4 (0.52 mL, 0.52 mmol) in toluene (5 mL). The
conversion of the acylsilane to the corresponding β-hydroxyacylsil-
ane required 4.5 h at –30 °C. The crude product was purified by
silica gel column chromatography with 8% ethyl acetate in hexane
(syn/anti) diastereoselectivity. 1H NMR (500 MHz, CDCl3): δ = 8.1 to afford pure liquid 3e (90 mg, 55% yield) as an inseparable mix-
(d, J = 8.5 Hz, 2 H), 7.54–7.51 (m, 2 H), 7.47–7.38 (m, 3 H), 7.29 ture with 96:4 (syn/anti) diastereoselectivity. 1H NMR (500 MHz,
(d, J = 8.4 Hz, 2 H), 5.06 (d, J = 2.9 Hz, 1 H), 4.8 (d, J = 6.5 Hz,
CDCl3): δ = 7.51–7.47 (m, 2 H), 7.42–7.34 (m, 3 H), 7.09–7.05 (m,
minor), 3.2 (br, 1 H), 3.13 (qd, J = 3.0, 7.3 Hz, 1 H), 0.81 (d, J = 2 H), 6.94–6.88 (m, 2 H), 4.9 (d, J = 3.7 Hz, 1 H), 4.63 (d, J =
7.3 Hz, 3 H), 0.54 (s, 3 H), 0.50 (s, 3 H), 0.49 (s, minor) 0.41 (d, J
= 4.1 Hz, minor) ppm. 13C NMR (75 MHz, CDCl3): δ = 250.8
(major), 149.3 (major), 146.9 (major), 133.8 (major), 133.4 (major),
130.2 (major), 130.0 (minor), 128.3 (major), 128.1 (minor), 126.9
7.9 Hz, minor), 3.27–3.2 (m, minor), 3.1 (qd, J = 3.7, 7.3 Hz, 1 H),
0.82 (d, J = 7.3 Hz, 3 H), 0.69 (d, J = 7.3 Hz, minor) 0.49 (s, 3 H),
0.46 (s, minor), 0.44 (s, 3 H), 0.38 (s, minor) ppm. 13C NMR
(125 MHz, CDCl3): δ = 250.7 (major), 162.8 (major), 160.8
(minor), 126.5 (major), 123.2 (major), 124.2 (minor), 71.1 (major), (major), 137.8 (major), 133.9 (major), 133.0 (minor), 130.1 (major),
70.9 (minor), 60.3 (minor), 55.4 (major), 14.1 (minor), 7.9 (major), 129.5 (minor), 128.3 (major), 127.8 (minor), 127.4 (major), 127.4
–4.6 (major), –4.9 (major) ppm. HRMS (ESI+): calcd. for (major), 115.0 (major), 114.8 (major), 71.3 (major), 56.2 (major),
C19H21O4NNaSi [M + Na]+ 366.1132; found 366.1133.
8.5 (major), –4.5 (major), –4.7 (major) ppm. HRMS (ESI+): calcd.
for C18H25O2NFSi [M + NH4]+ 334.1633; found 334.1630.
1-[Dimethyl(phenyl)silyl]-3-hydroxy-2-methyl-3-(3-nitrophenyl)prop-
an-1-one (3c): By the general experimental procedure for the prepa-
ration of β-hydroxyacylsilanes, the reaction was performed with 1
(100 mg, 0.52 mmol), 3-nitrobenzaldehyde (78 mg, 0.52 mmol) and
1-[Dimethyl(phenyl)silyl]-3-(4-chlorophenyl)-3-hydroxy-2-methyl-
propan-1-one (3f): By the general experimental procedure for the
preparation of β-hydroxyacylsilanes, the reaction was performed
TiCl4 (0.52 mL, 0.52 mmol) in toluene (5 mL). The conversion of with 1 (100 mg, 0.52 mmol), 4-chlorobenzaldehyde (73 mg,
the acylsilane to the corresponding β-hydroxyacylsilane required
5 h at –30 °C. The crude product was purified by silica gel column
chromatography with 10% ethyl acetate in hexane to afford pure
liquid 3c (110 mg, 65% yield) as an inseparable mixture with 95:5
0.52 mmol) and TiCl4 (0.52 mL, 0.52 mmol) in toluene (5 mL). The
conversion of the acylsilane to the corresponding β-hydroxyacylsil-
ane required 4 h at –30 °C. The crude product was purified by silica
gel column chromatography with 8% ethyl acetate in hexane to
(syn/anti) diastereoselectivity. 1H NMR (300 MHz, CDCl3): δ = 8.1 afford pure liquid 3f (110 mg, 65% yield) as an inseparable mixture
(d, J = 8.1 Hz, 1 H), 7.9 (s, 1 H), 7.54–7.30 (m, 7 H), 5.0 (d, J = with 89:11 (syn/anti) diastereoselectivity. 1H NMR (500 MHz,
2.9 Hz, 1 H), 4.75 (d, J = 7.0 Hz, minor), 3.23 (br, 1 H), 3.12 (qd,
CDCl3): δ = 7.4–7.36 (m, 2 H), 7.33–7.23 (m, 4 H), 7.09 (d, J =
4
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Stereoselective TiCl4-Mediated Aldol Reactions
8.3 Hz, 2 H), 6.92 (d, J = 8.3 Hz, 2 H), 4.79 (d, J = 3.5 Hz, 1 H), hydroxyacylsilanes, the reaction was performed with 1 (100 mg,
4.51 (d, J = 7.7 Hz, minor), 3.15–3.08 (m, minor), 2.97 (qd, J = 0.52 mmol), isobutyraldehyde (0.05 mL, 0.52 mmol) and TiCl4
3.5, 7.3 Hz, 1 H), 0.98 (d, J = 7.1 Hz, minor), 0.71 (d, J = 7.3 Hz, (0.52 mL, 0.52 mmol) in toluene (5 mL). The conversion of the
3 H), 0.63 (d, J = 7.3 Hz, minor), 0.39 (s, 3 H), 0.37 (s, minor),
0.35 (s, 3 H), 0.27 (s, minor) ppm. 13C NMR (125 MHz, CDCl3): δ
= 251.6 (minor), 250.6 (major), 141.2 (minor), 140.5 (major), 134.0
(minor), 133.9 (major), 133.84 (minor), 133.0 (major), 132.8
(major), 130.1 (major), 128.4 (minor), 128.3 (major), 128.2 (major),
127.8 (minor), 127.7 (minor), 127.2 (major), 75.7 (minor), 71.2
(major), 60.2 (minor), 56.0 (major), 29.8 (minor), 12.9 (minor), 8.3
(major), 0.2 (minor), –4.4 (major), –4.7 (major) ppm. HRMS
(ESI+): calcd. for C18H25O2NClSi [M + NH4]+ 350.1337; found
350.1330.
acylsilane to the corresponding β-hydroxyacylsilane required 2 h
at –30 °C. The crude product was purified by silica gel column
chromatography with 6% ethyl acetate in hexane to afford pure
liquid 3j (40 mg, 35% yield) as an inseparable mixture with 98:2
1
(syn/anti) diastereoselectivity. H NMR (500 MHz, CDCl3): δ =
7.55–7.51 (m, 2 H), 7.43–7.34 (m, 3 H), 3.5 (dd, J = 2.5, 8.5 Hz,
minor), 3.36 (dd, J = 2.5, 8.5 Hz, 1 H), 3.14–3.08 (m, minor), 2.6
(qd, J = 2.5, 7.1 Hz, 1 H), 2.30 (br, 1 H), 1.57–1.47 (m, 1 H), 0.92–
0.86 (m, 6 H), 0.69 (d, J = 6.7 Hz, 3 H), 0.55 (s, minor), 0.51 (d, J
= 1.1 Hz, 6 H), 0.39 (s, minor) ppm. 13C NMR (125 MHz, CDCl3):
δ = 250.4 (major), 134.3 (major), 133.9 (major), 133.2 (minor),
133.0 (minor), 130.0 (major), 129.2 (minor), 128.3 (major), 127.8
(minor), 74.8 (major), 51.3 (major), 30.6 (major), 29.8 (minor), 19.2
(major), 19.0 (major), 7.5 (major), –2.3 (minor), –4.2 (major), –4.3
( m a j o r ) p p m . H R M S ( E S I + ) : c a l c d . fo r C 1 5 H 2 4 O 2 -
NaSi [M + Na]+ 287.1437; found 287.1437.
1-[Dimethyl(phenyl)silyl]-3-hydroxy-3-(3-methoxyphenyl)-2-methyl-
propan-1-one (3g): By the general experimental procedure for the
preparation of β-hydroxyacylsilanes, the reaction was performed
with 1 (100 mg, 0.52 mmol), 3-methoxybenzaldehyde (0.063 mL,
0.52 mmol) and TiCl4 (0.52 mL, 0.52 mmol) in toluene (5 mL). The
conversion of the acylsilane to the corresponding β-hydroxyacylsil-
ane required 3 h at –30 °C. The crude product was purified by silica
gel column chromatography with 10% ethyl acetate in hexane to
afford pure liquid 3g (120 mg, 75% yield) as an inseparable mixture
with 94:6 (syn/anti) diastereoselectivity. 1H NMR (500 MHz,
CDCl3): δ = 7.54–7.46 (m, 2 H), 7.44–7.31 (m, 3 H), 7.14 (t, J =
7.8 Hz, 1 H), 6.78–6.64 (m, 3 H), 4.91 (d, J = 3.4 Hz, 1 H), 4.62
(d, J = 7.9 Hz, minor), 3.87 (s, minor), 3.77 (s, minor), 3.75 (s, 3
H), 3.32–3.25 (m, minor), 3.14 (qd, J = 3.5, 7.1 Hz, 1 H), 1.28 (s,
minor), 0.83 (d, J = 7.2 Hz, 3 H), 0.71 (d, J = 7.2 Hz, minor), 0.57
(s, minor), 0.49 (s, 3 H), 0.47 (s, minor), 0.45 (s,3 H), 0.38 (s, minor)
ppm. 13C NMR (125 MHz, CDCl3): δ = 250.6 (major), 159.5
(major), 143.8 (major), 134.1 (minor), 133.9 (major), 133.4 (minor),
133.0 (major), 129.8 (minor), 129.2 (minor), 129.0 (major), 128.3
(major), 128.1 (minor), 118.8 (minor), 118.1 (major), 113.2 (minor),
71.7 (major), 56.2 (major), 54.9 (major), 29.0 (minor), 8.4 (major),
–2.8 (minor), –4.4 (major), –4.6 (major) ppm. HRMS (ESI+):
calcd. for C19H24O3NaSi [M + Na]+ 351.1386; found 351.1384.
1-[Dimethyl(phenyl)silyl]pentane-1-one (4): Purified with 4 %
EtOAc/hexane to afford 4 as a light yellow oil in 80% yield. IR: ν
˜
= 2930, 2872, 1644, 1428, 1250, 1111, 1052, 817, 782, 734, 700,
467 cm–1. 1H NMR (300 MHz, CDCl3): δ = 7.59–7.52 (m, 2 H),
7.44–7.34 (m, 3 H), 2.57 (t, J = 7.1 Hz, 2 H), 1.52–1.36 (m, 2 H),
1.25–1.13 (m, 2 H), 0.81 (t, J = 7.1 Hz, 3 H), 0.49 (s, 6 H) ppm.
13C NMR (75 MHz CDCl3): δ = 246.5, 134.5, 133.8, 129.7, 128.0,
48.4, 24.1, 22.2, 13.7, –4.8 ppm. HRMS (ESI+): calcd. for
C13H20ONaSi [M + Na]+ 243.1235; found 243.1234.
1-[Dimethyl(phenyl)silyl]pent-4-en-1-one (5): Purified with 4 %
EtOAc/hexane to afford 5 as a colourless oil in 70% yield. IR: ν =
˜
3075, 2924, 2857, 1644, 1433, 1237, 1116, 913, 848, 770 cm–1. 1H
NMR (500 MHz, CDCl3): δ = 7.55–7.51 (m, 2 H), 7.41–7.34 (m, 3
H), 5.75–5.65 (m, 1 H), 4.93–4.85 (m, 2 H), 2.67 (t, J = 7.1 Hz, 2
H), 2.2 (td, J = 7.0, 6.5 Hz, 2 H), 0.49 (s, 6 H) ppm. 13C NMR
(75 MHz, CDCl3): δ = 245.0, 137.2, 134.2, 133.8, 129.8, 128.0,
114.7, 47.6, 26.1, –4.8, –4.9 ppm. HRMS (ESI+): calcd. for
C13H18ONaSi [M + Na]+ 241.1000; found 241.1010.
1-[Dimethyl(phenyl)silyl]-3-hydroxy-2-methyl-3-p-tolylpropan-1-one
(3h): By the general experimental procedure for the preparation of
β-hydroxyacylsilanes, the reaction was performed with 1 (100 mg,
0.52 mmol), 4-methylbenzaldehyde (0.06 mL, 0.52 mmol), TiCl4
(0.52 mL, 0.52 mmol) in toluene (5 mL). The conversion of the
acylsilane to the corresponding β-hydroxyacylsilane required 9 h
at –30 °C. The crude product was purified by silica gel column
chromatography with 8% ethyl acetate in hexane to afford pure
liquid 3h (45 mg, 30% yield) as an inseparable mixture with 81:19
4-(Benzyloxy)-1-[dimethyl(phenyl)silyl]butan-1-one (6): Purified
with 10% EtOAc/hexane to afford 6 as a colourless oil in 85%
yield. IR: ν = 3068, 2956, 2858, 1643, 1428, 1249, 1110, 835, 776,
˜
735, 698 cm–1 1H NMR (300 MHz, CDCl3): δ = 7.54 (d, J =
.
7.3 Hz, 2 H), 7.42–7.23 (m, 8 H), 4.26 (s, 2 H), 3.20 (t, J = 6.2 Hz,
2 H), 2.5 (t, J = 7.1 Hz, 2 H), 1.84–1.73 (m, 2 H) ppm. 13C NMR
(125 MHz, CDCl3): δ = 245.5, 138.4, 134.4, 133.9, 129.8, 128.2,
128.1, 127.5, 127.4, 72.6, 69.3, 45.2, 22.1, –4.8 ppm. HRMS (ESI+):
calcd. for C19H24O2NaSi [M + Na]+ 335.1437; found 335.1432.
1
(syn/anti) diastereoselectivity. H NMR (300 MHz, CDCl3): δ =
7.58–7.49 (m, 2 H), 7.48–7.33 (m, 4 H), 7.17–7.01 (m, 4 H), 4.96
(d, J = 3.2 Hz, 1 H), 4.68 (d, J = 7.9 Hz, minor), 3.37–3.25 (m,
minor), 3.17 (qd, J = 3.3, 7.1 Hz, 1 H), 2.36 (s, minor), 2.1 (s, 3
H), 0.85 (d, J = 7.1 Hz, 3 H), 0.71 (d, J = 7.3 Hz, minor), 0.6 (s,
minor), 0.48 (d, J = 10 Hz, 6 H), 0.42 (s, minor) ppm. 13C NMR
(125 MHz, CDCl3): δ = 252.1 (minor), 251.3 (major), 139.5
(minor), 139.0 (major), 137.2 (minor), 136.5 (major), 134.1 (minor),
133.9 (major), 133.8 (minor), 133.0 (major), 130.2 (minor), 130.0
(major), 129.8 (minor), 129.5 (minor), 128.9 (minor), 128.7 (major),
128.2 (major), 126.4 (minor), 125.7 (major), 76.3 (minor), 71.8
(major), 56.2 (major), 21.3 (minor), 21.1 (major), 11.3 (minor), 8.3
(major), –4.5 (major), –4.61 (minor), –4.7 (major) ppm. HRMS
(ESI+): calcd. for C19H24O2NaSi [M + Na]+ 335.1437; found
335.1430.
1-[Dimethyl(phenyl)silyl]-3-phenylpropane-1-one (7): Purified with
4% EtOAc/hexane to afford 7 as a colourless oil in 80% yield. IR:
ν = 3068, 3025, 2956, 1644, 1427, 1250, 1111, 814, 781, 734,
˜
699 cm–1. 1H NMR (300 MHz, CDCl3): δ = 7.59–7.47 (m, 3 H),
7.43–7.34 (m, 4 H), 7.25–7.15 (m, 2 H), 7.07 (d, J = 6.8 Hz, 2 H),
2.94–2.85 (m, 2 H), 2.82–2.74 (m, 2 H), 0.48 (s, 6 H) ppm. 13C
NMR (75 MHz, CDCl3): δ = 245.1, 141.4, 134.2, 133.9, 129.9,
128.3, 128.2, 127.7, 125.8, 50.3, 28.2, –4.8, –4.9 ppm. HRMS
(ESI+): calcd. for C17H20ONaSi [M + Na]+ 291.1175; found
291.1176.
General Experimental Procedure for the Preparation of β-Hydroxy-
acylsilanes: A 1 m solution of TiCl4 in toluene was added dropwise
to a mixture of acylsilane (100 mg) and aldehyde in toluene (5 mL)
under a nitrogen atmosphere at –30 °C, and the reaction mixture
was stirred at the same temperature. After completion of the reac-
tion, a saturated NH4Cl solution was added, and the reaction mix-
1-[Dimethyl(phenyl)silyl]-3-hydroxy-2,4-dimethylpentan-1-one (3j):
By the general experimental procedure for the preparation of β-
Eur. J. Org. Chem. 0000, 0–0
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G. Marri, J. S. Reddy, J. Ruiz, S. Das, R. Grée
FULL PAPER
ture was warmed to room temperature. The mixture was extracted
with EtOAc (2ϫ10 mL), and the organic phases were dried with
anhydrous Na2SO4, filtered and concentrated in vacuo. The residue
was purified by silica gel column chromatography (100–200 mesh).
1
(syn/anti) diastereoselectivity. H NMR (300 MHz, CDCl3): δ =
7.48 (d, J = 7.7 Hz, 2 H), 7.42–7.16 (m, 17 H), 7.11 (d, J = 6.6 Hz,
2 H), 4.77 (d, J = 5.0 Hz, 1 H), 4.69 (d, J = 8.14 Hz, minor), 4.47
(s, minor), 4.24 (s, 2 H), 4.2 (s, minor), 3.55–3.44 (m, 1 H), 3.22–
3.11 (m, 2 H), 2.59 (br, 1 H), 2.0–1.8 (m, 1 H), 1.7–1.6 (m, 1 H),
0.4 (s, minor), 0.35 (s, 3 H), 0.31 (s, minor), 0.28 (s, 3 H) ppm. 13C
NMR (75 MHz, CDCl3): δ = 250.8 (major), 142.9 (minor), 141.9
(major), 137.9 (major), 134.2 (minor), 134.1 (major), 133.7 (minor),
129.9 (major), 129.7 (minor), 129.3 (minor), 128.8 (minor), 128.2
(major), 128.2 (major), 127.9 (minor), 127.6 (major), 127.5 (major),
127.2 (major), 126.1 (major), 75.7 (minor), 72.4 (major), 71.9
(major), 68.2 (major), 67.4 (minor), 59.0 (major), 57.3 (minor), 28.5
(minor), 25.5 (major), –4.8 (minor), –4.9 (major), –5.1 (minor), –5.3
(major) ppm. HRMS (ESI+): calcd. for C26H30O3NaSi [M + Na]+
441.1856; found 441.1841.
1-[Dimethyl(phenyl)silyl]-2-[hydroxy(phenyl)methyl]pentane-1-one
(8a): By the general experimental procedure for the preparation of
β-hydroxyacylsilanes, the reaction was performed with 4 (100 mg,
0.45 mmol), benzaldehyde (0.046 mL, 0.45 mmol) and TiCl4
(0.45 mL, 0.45 mmol) in toluene (5 mL). The conversion of the
acylsilane to the corresponding β-hydroxyacylsilane required 3 h
at –30 °C. The crude product was purified by silica gel column
chromatography with 8% ethyl acetate in hexane to afford liquid 8a
(100 mg, 70% yield) as an inseparable mixture with 83:17 (syn/anti)
1
diastereoselectivity. H NMR (500 MHz, CDCl3): δ = 7.38 (d, J =
6.7 Hz, 2 H), 7.3–6.9 (m, 9 H), 6.96 (d, J = 7.3 Hz, 2 H), 5.8 (d, J
= 15.0 Hz, minor), 4.83 (d, J = 3.3 Hz, minor), 4.58 (d, J = 4.6 Hz,
1 H), 4.53 (d, J = 6.8 Hz, minor), 3.3 (t, J = 6.4 Hz, minor), 3.19
(m, 1 H), 3.02 (qd, J = 7.1, 3.5 Hz, minor), 1.53–1.43 (m, 1 H),
1.2–1.1 (m, 1 H), 0.9–0.68 (m, 2 H), 0.56 (t, J = 7.2 Hz), 0.37 (s,
1-[Dimethyl(phenyl)silyl]-2-benzyl-3-hydroxy-3-phenylpropan-1-one
(11a): By the general experimental procedure for the preparation of
β-hydroxyacylsilanes, the reaction was performed with 7 (100 mg,
0.37 mmol), benzaldehyde (0.038 mL, 0.37 mmol) and TiCl4
(0.37 mL, 0.37 mmol) in toluene (5 mL). The conversion of the
acylsilane to the corresponding β-hydroxyacylsilane required 6 h
at –30 °C. The crude product was purified by silica gel column
chromatography with 7% ethyl acetate in hexane to afford liquid
11a (58 mg, 45% yield) as an inseparable mixture with 99:01
(syn/anti) diastereoselectivity. 1H NMR (300 MHz, CDCl3): δ =
8.04–7.61 (m, 16 H) 7.52–7.41 (m, 2 H), 5.75 (d, J = 3.5 Hz, minor),
5.21 (d, J = 4.9 Hz, 1 H), 4.67 (q, J = 7.1 Hz, minor), 4.32–4.27
(m, 1 H), 3.59–3.44 (m, 1 H), 3.25 (dd, J = 3.5, 3.3 Hz, 1 H), 2.99–
2.75 (br, 1 H), 1.99 (s, minor), 1.00 (s, minor), 0.96 (s, minor), 0.67
(s, minor), 0.63 (s, 3 H), 0.57 (s, minor), 0.45 (s, 3 H) ppm. 13C
NMR (75 MHz, CDCl3): δ = 254.6 (major), 141.5 (major), 139.5
(major), 134.1 (major), 133.5 (major), 129.8 (major), 129.2 (major),
128.3 (major), 128.0 (major), 127.4 (major), 126.1 (major), 126.0
(major), 72.5 (major), 63.0 (major), 32.2 (major), –5.8 (major), –6.1
(major) ppm. HRMS (ESI+): calcd. for C24H26O2NaSi [M + Na]+
397.1594; found 397.1606.
minor), 0.33 (s, minor), 0.32–0.23 (m, 6 H), 0.2 (s, minor) ppm. 13
C
NMR (75 MHz, CDCl3): δ = 253.1 (major), 251.5 (minor), 142.0
(major), 141.9 (minor), 134.1 (major), 133.9 (major), 133.8 (minor),
132.9 (minor), 130.0 (major), 128.1 (major), 127.8 (minor), 127.4
(minor), 127.1 (major), 127.0 (minor), 125.9 (major), 125.8 (major),
75.3 (minor), 72.0 (major), 71.8 (minor), 61.4 (major), 60.6 (minor),
56.1 (major), 55.8 (minor), 30.1 (minor), 27.2 (major), 21.0 (major),
20.2 (minor), 14.3 (major), 14.0 (minor), –5.0 (major), –5.2 (major)
ppm. HRMS (ESI+): calcd. for C20H26O2NaSi [M + Na]+
349.1594; found 349.1599.
1-[Dimethyl(phenyl)silyl]-2-[hydroxy(phenyl)methyl]pent-4-ene-1-one
(9a): By the general experimental procedure for the preparation of
β-hydroxyacylsilanes, the reaction was performed with 5 (100 mg,
0.45 mmol), benzaldehyde (0.046 mL, 0.45 mmol) and TiCl4
(0.45 mL, 0.45 mmol) in toluene (5 mL). The conversion of the
acylsilane to the corresponding β-hydroxyacylsilane required 5 h
at –30 °C. The crude product was purified by silica gel column
chromatography with 8% ethyl acetate in hexane to afford pure
liquid 9a (90 mg, 60% yield) as an inseparable mixture with 84:16
Supporting Information (see footnote on the first page of this arti-
cle): experimental procedures, spectroscopic data and NMR spec-
tra.
1
(syn/anti) diastereoselectivity. H NMR (500 MHz, CDCl3): δ =
7.54–7.5 (m, 2 H), 7.5–7.4 (m, 4 H), 7.34–7.23 (m, 4 H), 7.17–7.13
(m, 2 H), 5.53–5.43 (m, 1 H), 4.92–4.82 (m, 2 H), 4.79 (d, J =
5.0 Hz, 1 H), 4.76 (d, J = 6.2 Hz, minor), 3.55–3.49 (m, 1 H), 3.25–
3.22 (m, minor), 2.73–2.68 (t, J = 7.4 Hz, minor), 2.61–2.56 (m,
minor), 2.46–2.38 (m, 1 H), 2.21–2.13 (m, 1 H), 2.09–2.02 (m,
minor), 0.45 (s, minor), 0.42 (s, 3 H), 0.41 (s, minor),0.36 (s, 3 H),
0.32 (s, minor) ppm. 13C NMR (125 MHz, CDCl3): δ = 252.4
(major), 142.8 (minor), 141.7 (major), 135.7 (major), 134.6 (minor),
134.2 (major), 133.7 (major), 132.9 (minor), 130.0 (major), 129.8
(minor), 128.3 (minor), 128.2 (major), 128.2 (major), 128.0 (minor),
127.3 (major), 126.1 (major), 126.1 (minor), 116.5 (major), 72.2
(major), 75.0 (minor), 60.9 (major), 59.9 (minor), 32.5 (minor), 29.9
(major), –5.1 (major), –5.3 (major) ppm. HRMS (ESI+): calcd. for
C20H24O2NaSi [M + Na]+ 347.1437; found 347.1448.
Acknowledgments
This research was performed as part of the Indo–French “Joint
Laboratory for Sustainable Chemistry at Interfaces”. The authors
thank the Centre National de la Recherche Scientifique (CNRS),
Council of Scientific and Industrial Research (CSIR) (12th Five
year Plan, ORIGIN: CSC-0108), University of Rennes 1 and the
Centre Franco-Indien pour la Promotion de la Recherche Avancée/
Indo-French Centre for the Promotion of Advanced Research (CE-
FIPRA/IFCPAR) for support of this research. J. S. R. thanks the
University Grants Commitee (UGC), New Delhi for financial as-
sistance. G. M. thanks CSIR for financial assistance.
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and TiCl4 (0.3 mL, 0.32 mmol) in toluene (5 mL). The conversion
of the acylsilane to the corresponding β-hydroxyacylsilane required
2 h at –30 °C. The crude product was purified by silica gel column
chromatography with 10% ethyl acetate in hexane to afford pure
liquid 10a (75 mg, 58% yield) as an inseparable mixture with 77:23
6
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Stereoselective TiCl4-Mediated Aldol Reactions
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[15] C. T. Clark, B. C. Milgram, K. A. Scheidt, Org. Lett. 2004, 6,
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[16] It should be noted that the same reaction can be performed
with other groups on silicon: with a triethylsilyl (TES) group,
the TiCl4-mediated reaction gave the aldols in 43% yield and
a 93:7 syn/anti ratio after 24 h under the same conditions. In
the same way, with a tert-butyldiphenylsilyl (TBDPS) group,
the aldol products were obtained in 66% yield and a 77:23
syn/anti ratio after 48 h.
[17] For this type of β-hydroxyacylsilane, the syn and anti isomers
are usually separable after protection of the hydroxy group as
a benzoate, acetate, tert-butyldimethylsilyl (TBS) or meth-
oxymethyl (MOM) group, for instance.
[7] For selected references, see: a) A. K. Ghosh, M. Onishi, J. Am.
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[8] For selected references, see: a) G. Helmchen, U. Leikauf, I.
Taufer-Knöpfel, Angew. Chem. Int. Ed. Engl. 1985, 24, 874;
Angew. Chem. 1985, 97, 874; b) W. Oppolzer, J. Marco-
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Received: September 26, 2014
Published Online: ᭿
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7

Job/Unit: O43263
/KAP1
Date: 15-12-14 13:03:59
Pages: 8
G. Marri, J. S. Reddy, J. Ruiz, S. Das, R. Grée
FULL PAPER
Synthetic Methods
G. Marri, J. S. Reddy, J. Ruiz, S. Das,*
R. Grée* ........................................... 1–8
Stereoselective TiCl4-Mediated Aldol Re-
actions Starting from Acylsilanes
A new, simple and efficient method has
been developed for the preparation of β-
hydroxyacylsilanes through a Lewis acid
mediated aldol condensation. The use of
TiCl4 under optimized reaction conditions
allows the preparation of the target mol-
ecules in fair-to-good yields with excellent
syn selectivities.
Keywords: Silanes / Aldol reactions / Sili-
con / Lewis acids
8
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